The challenge generated by the various large scale genome projects is to derive biologically relevant information from the primary DNA sequences. In the past few years, a number of approaches to mine this information have emerged. These can be divided into Expression Genomics, Proteomics, Information Genomics, and Functional Genomics. Perhaps, the most promising Functional Genomics approach is based on the double strand RNA (dsRNA) methodology. In several organisms, introduction of a dsRNA has proven to be an effective tool to suppress gene expression through a process referred to as RNA interference (RNAi). Importantly, the simple addition of dsRNA to Drosophila cells in culture reduces or eliminates the expression of target genes by RNAi, thus phenocopying loss-of-function mutations. This property of Drosophila cells make it possible to develop high throughput RNAi screens in 384-well plates to efficiently and systematically test the function of all 14,000 Drosophila genes in specific cell-based assays. In the past few years, we have developed such a methodology and the goal of this proposal is to establish an infrastructure within the Institute of Chemistry and Cell biology at Harvard Medical School (ICCB/HMS) that will make this approach available to the entire community. Specifically, we propose to establish an "RNAi facility" where visiting scientists will be hosted to conduct RNAi screens with help of experienced staff. The facility will provide bioinformatic support to help investigators conduct the screens and interpret the primary data. In addition, a central database will be established that keeps records of all RNAi screens. The results generated by the "RNAi facility" will become a public database, and thus provide a discovery vehicle to generate hypothesis driven research. Finally, to demonstrate the value of the approach, we describe a number of cell-based screens that will identify genes involved in cell survival, cytokinesis, cell shape changes and immunity.